Journal of Ginseng Research

The Korean Society of Ginseng (고려인삼학회)
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Ginsenoside Rb1 attenuates methamphetamine (METH)-induced neurotoxicity through the NR2B/ERK/CREB/BDNF signalings in vitro and in vivo models

  • Yang, Genmeng (NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University) ;
  • Li, Juan (School of Basic Medicine, Kunming Medical University) ;
  • Peng, Yanxia (NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University) ;
  • Shen, Baoyu (NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University) ;
  • Li, Yuanyuan (NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University) ;
  • Liu, Liu (NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University) ;
  • Wang, Chan (NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University) ;
  • Xu, Yue (NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University) ;
  • Lin, Shucheng (NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University) ;
  • Zhang, Shuwei (NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University) ;
  • Tan, Yi (NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University) ;
  • Zhang, Huijie (NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University) ;
  • Zeng, Xiaofeng (NHC Key Laboratory of Drug Addiction Medicine, Kunming Medical University) ;
  • Li, Qi (SDIVF R&D Centre) ;
  • Lu, Gang (CUHK-SDU Joint Laboratory on Reproductive Genetics, School of Biomedical Sciences, the Chinese University of Hong Kong)
  • Received : 2021.03.31
  • Accepted : 2021.07.09
  • Published : 2022.05.01
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Abstract

Aim: This study investigates the effects of ginsenoside Rb1 (GsRb1) on methamphetamine (METH)-induced toxicity in SH-SY5Y neuroblastoma cells and METH-induced conditioned place preference (CPP) in adult Sprague-Dawley rats. It also examines whether GsRb1 can regulate these effects through the NR2B/ERK/CREB/BDNF signaling pathways. Methods: SH-SY5Y cells were pretreated with GsRb1 (20 mM and 40 mM) for 1 h, followed by METH treatment (2 mM) for 24 h. Rats were treated with METH (2 mg/kg) or saline on alternating days for 10 days to allow CPP to be examined. GsRb1 (5, 10, and 20 mg/kg) was injected intraperitoneally 1 h before METH or saline. Western blot was used to examine the protein expression of NR2B, ERK, P-ERK, CREB, P-CREB, and BDNF in the SH-SY5Y cells and the rats' hippocampus, nucleus accumbens (NAc), and prefrontal cortex (PFC). Results: METH dose-dependently reduced the viability of SH-SY5Y cells. Pretreatment of cells with 40 µM of GsRb1 increased cell viability and reduced the expression of METH-induced NR2B, p-ERK, p-CREB and BDNF. GsRb1 also attenuated the expression of METH CPP in a dose-dependent manner in rats. Further, GsRb1 dose-dependently reduced the expression of METH-induced NR2B, p-ERK, p-CREB, and BDNF in the PFC, hippocampus, and NAc of rats. Conclusion: GsRb1 regulated METH-induced neurotoxicity in vitro and METH-induced CPP through the NR2B/ERK/CREB/BDNF regulatory pathway. GsRb1 could be a therapeutic target for treating METH-induced neurotoxicity or METH addiction.

Keywords

Acknowledgement

We acknowledge Yang G.M., Li J., PENG Y.X., Wang S.W., Shen B.Y., Li Y.Y., Liu L., Wang C., Xu Y., Lin S.C., Zhang S.W., Tan Y.I., and Zhang F.J. for their participated in this work's literature search, experimental validation, data analysis, and manuscript writing. Zeng X.F., Li Q., and Lu G. supervised the study design and critically read and edited the manuscript. All the authors approved the final version for publication.

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